Pharmacokinetic Properties of 200 and 400 mg Acyclovir Tablet in Indonesia Healthy Subject

Twenty-eight healty subjects were given a single dose of acyclovir tablet or Zovirax® in dosage form 200 mg and 400mg with 240 mL of water. Then the blood samples for acyclovir was drawn and analyzed using LCMS/MS. All subjects sample plasma were analyzed for pharmacokinetic evaluation

• Acyclovir 200 MG (Drug): Administered with 240 mL of water
• Acyclovir 400 MG (Drug): Administered with 240 mL of water
• Zovirax 200 MG Tablet (Drug): Administered with 240 mL of water
• Zovirax 400 MG Tablet (Drug): Administered with 240 mL of water

Primary outcomes

• Pharmacokinetics Parameter [before dosing (0 h) and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours after dosing]: Maximum plasma concentration (Cmax)
• Pharmacokinetics Parameter [Predose at (0 h) and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours post dose]: Area Under Curve from 0 to 24 hours (AUCt)

Secondary outcomes

• Geometric Mean Ratio [before dosing (0 h) and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours after dosing]: The ratio between maximum concentration of test drug and reference drug after drug administration
• Geometric Mean Ratio [before dosing (0 h) and at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours after dosing]: The ratio between area under curve from 0 to 24 hours of test drug and reference drug

Sex: All, ages: 18 Years to 55 Years, accepts healthy volunteers

Inclusion Criteria:

* body weight within normal range (body mass index between 18 and 25 kg/m2)
* had normal blood pressure (systolic was ranged between 90 to 120 mmHg and diastolic was ranged between 60 to 80 mmHg)
* had normal electrocardiogram
* absence of significant disease or clinically significant abnormal laboratory values on laboratory evaluation, medical history or physical examination during screening

Exclusion Criteria:

* pregnant women
* nursing mothers
* women of childbearing potential without adequate contraception
* had a history of contraindication or hypersensitivity to aciclovir, or other antiviral or other ingredients in the study products or a history of serious allergic reaction to any drug,
* a significant allergic disease, or allergic reaction; presence of medical condition which might significantly influence the pharmacokinetics of the study drug, e.g. chronic gastrointestinal disease, diarrhea, gastric surgery, renal insufficiency, hepatic dysfunction or cardiovascular disease
* presence of any coagulation disorder or clinically significant hematology abnormalities; using any medication (prescription or non-prescription drug, food supplement, herbal medicine)
* particularly the medication known to affect the pharmacokinetics of the study drug
* who had participated in any clinical study within 3 months prior to the study (< 90 days)
* subjects who had donated or lost 300 ml (or more) of blood within 3 months prior to the study
* who were positive to HIV, HBsAg, and HCV tests
* who were unlikely to comply with the protocol, e.g uncooperative attitude, inability to return for follow up visits
* poor venous access; and who smoked more than 10 cigarettes a day
* had a history of drug or alcohol abuse within 12 months prior to screening for this study and who were unlikely to comply with the protocol, e.g uncooperative attitude, inability to return for follow up visits, poor venous access

Participant flow

Outcome results

• Pharmacokinetics Parameter (Primary), Mean, ng/mL: Acyclovir 200 mg Tablet 613.21 +/- 244.06; Zovirax® 200 mg Tablet 675.58 +/- 258.18; Acyclovir 400 mg Tablet 807.13 +/- 278.85; Zovirax® 400 mg Tablet 882.89 +/- 351.97
• Pharmacokinetics Parameter (Primary), Mean, ng*h/mL: Acyclovir 200 mg Tablet 3609.80 +/- 1425.19; Zovirax® 200 mg Tablet 3865.20 +/- 1339.05; Acyclovir 400 mg Tablet 4583.29 +/- 1518.93; Zovirax® 400 mg Tablet 5088.28 +/- 1758.74
• Geometric Mean Ratio (Secondary), Geometric mean, percentage: Acyclovir 200 mg Tablet 90.65 (82.69 to 99.37); Zovirax® 200 mg Tablet 90.65 (82.69 to 99.37); Acyclovir 400 mg Tablet 93.63 (84.85 to 103.33); Zovirax® 400 mg Tablet 93.63 (84.85 to 103.33)
• Geometric Mean Ratio (Secondary), Geometric mean, percentage: Acyclovir 200 mg Tablet 92.74 (86.04 to 99.96); Zovirax® 200 mg Tablet 92.74 (86.04 to 99.96); Acyclovir 400 mg Tablet 90.10 (80.80 to 100.48); Zovirax® 400 mg Tablet 90.10 (80.80 to 100.48)

Adverse events

Time frame: before dosing (0 h) at 15, 30, 45 minutes, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16 and 24 hours after dosing

Other adverse events by term

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• Study Protocol and Statistical Analysis Plan (PDF, 2019-12-13)

• Metta Sinta Sari Wiria, Principal investigator, PT Pharma Metric Labs
• I Gusti Putu Bagus Diana Virgo, Study director, PT Pharma Metric Labs